Andrea Alimonti, MD Curriculum Vitae General Information Date prepared: Home Address: Telephone: (+39) 328 437 3942 Place of Birth: Date of Birth: Actual Position: Head, Molecular Oncology Institute of Oncology Research Oncology Institute of Southern Switzerland
2000 MD degree, Magna Cum Laude (GPA: 110/110) University of Rome “La Sapienza” Rome, Italy Dissertation Topic: Capecitabine and Oxaliplatin in advanced colorectal cancer: a dose-finding study
2004 Residency in Clinical Oncology, Magna Cum Laude Regina Elena National Cancer Institute, Rome, Italy Dissertation Topic: PI3K/ PTEN/AKT pathway in malignant transformation and drug resistance Postdoctoral Training: BIDMC-Harvard Medical School
Position: Postdoctoral Clinical/Research Fellow
Memorial Sloan-Kettering Cancer Center
Position: Postdoctoral Clinical/Research Fellow
Regina Elena National Cancer Institute of Rome
Division of Medical Oncology: Prof. Francesco Cognetti
Internships: San Pietro Hospital Fatebenefratelli University of Rome “La Sapienza” Fellowships, Grants and Awards:
European Research Council (ERC) starting Grant
Marie Curie International Reintegration Grant (IRG)
European Society of Medical Oncology (ESMO) Award in Translational Research.
Susan Komen Breast Cancer Foundation (Komen Italia)
Italian Association of Clinical Oncology (AIOM)
Scientific and Medical Societies:
2005 Full Member of the European Society of Medical Oncology (ESMO) 2004 Full Member of the Italian Association of Clinical Oncology (AIOM)
Ad hoc reviewer for the Journal of Clinical Oncology (JCO), Clinical Cancer Research, European Journal of Cancer and Cancer Chemotherapy and Pharmacology Major Research interest:
2. Prostate Cancer 3. PTEN/PI3K/AKT pathway
4. Targeted therapies 5. Oncogene Induced Senescence
International Application No.:PCT/US2008/078972 (WO/2009/046436).
Methods for inhibiting senescence of epithelial cells. (Alimonti A. & Pandolfi PP.) Additional Information:
2001 – 2002 Author of an electronic computerized CD-card for the storage of medical files and treatment-related-information for cancer patients -D.H. Osp. San Pietro Fatebenefratelli, Rome, Italy.
Languages Part II: Research and Clinical Contributions A. Narrative report of Research Contributions
I began working in clinical oncology approximately six years ago when the therapeutic approach to patient care was dramatically shifting from clinic to laboratory, where novel therapies were being developed to antagonize specific genetic alterations in tumors. For this reason, I choose to pursue academic research and joined one of the most prestigious cancer laboratories in the U.S first at Memorial Sloan-Kettering Cancer Center and later at Harvard Medical School. Over the past four years, I learned the principles of basic cancer genetics and had the opportunity to use unique mouse models for the development of novel cancer treatment and identification of their mechanism of action. During these years I have actively worked in understanding the molecular mechanism that drives Pten breast and prostate tumorigenesis. Since the beginning of my experience working at the lab, I have been in charged of developing several pre-clinical trials and studying different compounds such as an analogue of Rapamyicin (RAD001), an inhibitor of MDM2 (Nutlin-3) and a novel PTEN inhibitor (VO-OHpic). The novelty of using mouse models harboring deletion of specific tumor suppressor or over-expression of known oncogenes relies on the possibility to test the activity of drugs that selectively target these alterations in vivo. Studying some of these compounds in a Pten prostate conditional mouse model, I have discovered a new therapeutic approach for cancer that has been named “pro-senescence” therapy. The innovation of this therapeutic approach consists in pushing the cancer stem cells towards senescence (an irreversible growth arrest) exhausting the pool of cells that can continuously regenerate cancer cells even after cytotoxic treatment. As a consequence of such discovery I have also filed a patent application.
B. Founding Information
European Research Council (ERC) starting Grant
European Society of Medical Oncology (ESMO) Research Grant
Marie Curie International Reintegration Grant
Department of Cancer Genetics, BIDMC Harvard Medical School, “Pre-clinical trial project”
Department of Medicine, Prostate Cancer Division, “MSKCC fellowship and career support”
2004-2006 Italian Association of Medical Oncologist fellowship
C. Report of Clinical Activities My clinical activity is actually focused on the coordination of all the clinical studies at the Day-Hospital of Oncology of my Institute. I’m at the moment in charge to follow two clinical trials, the H3E-EW-B012 "FRAME” trial (our center is the National Coordinator of the project) and the “3144A2 3005 WW Study” testing the oral her-2
inhibitor, neratinib, in combination with paclitaxel, versus standard therapy with trastuzumab (Herceptin) in combination with paclitaxel, for first-line treatment of her-2+ metastatic breast cancer. During my residency in clinical oncology at the National Cancer Institute of Rome, I have been involved in multiple clinical activities both at the Department and at the Day-Hospital (D.H.) of Oncology. I was in charge, together with other two residents, of all the clinical activities including: medical visits, decision and scheduling of chemotherapies and patient demission. The medical department was composed of 25 beds, the D.H. served almost 60 patients per day. The D.H. was divided in different medical teams, mainly, breast, prostate, colon and lung cancer, composed by one resident and one senior medical assistant. I was in charge of following patients affected by breast and prostate cancer. During this period, I was responsible to follow several phase III clinical trials. I have been one of the study coordinators for my Institute of TAXIT 216 trial, which aimed to assess the efficacy of adding docetaxel in a block-sequential fashion to a regimen with doxorubicin followed by CMF in the adjuvant therapy for node-positive early stage breast cancer.
Regional, National, and international Contribution Invited Lectures: 2011TAT 2011 International Symposium on targeted anticancer therapies Speaker: Alimonti A. PTEN loss induced cellular senescence for "Pro- senescence" therapy for cancer. 2011 Oncology Institute of Southern Switzerland Speaker: Alimonti A. Manipulation of senescence pathway for cancer therapy 2011 Molecular Biotechnology Center, University of Turin Speaker: Alimonti A. Manipulation of senescence pathway for cancer therapy: from experimental models to clinic 2010 SOLTI Innovative Breast Cancer Research Conference Speaker: Alimonti A. Triple negative Breast Cancer biology 2010 Institute of Research in Biomedicine (IRB) Barcelona Speaker: Alimonti A. PTEN dosage in cancer initiation and progression 2004 Osp. San Pietro Fatebenefratelli, Rome, Italy. Design and coordination of the anti-smoking campaign Speaker: Alimonti A. Design and coordination of the anti-smoking campaign “Scuola Senza Fumo” 2003 V International Congress of The Ageing Society, Rome, Italy Montecitorio Eventi, (Italian Parliament), Speakers: Alimonti A, Monorchio A, Alimonti P. Air pollution and Health Effects 2002 Osp. San Pietro Fatebenefratelli, Rome, Italy Speaker: Alimonti A. New tools to improve the informatization and the quality of assistance of an Oncology Departement. Poster display presentations:
2009 IMPAKT 2009 Breast Cancer Conference, Brussels, Belgium
Speaker: A. Alimonti. Abstract: Andrea Alimonti. A subtle variation in PTEN dosage confers breast cancer susceptibility: The “no hit“hypotesis for tumor suppressor genes. (Travel Grant awarded) 2007 15 SPORE Investigators Workshop in Translational Cancer Research Speaker: A. Alimonti. Abstract: Andrea Alimonti, Peter T. Scardino, Pier Paolo Pandolfi. Pharmacologic Modulators of Cellular Senescence. 2004 American Association for Cancer Research (AACR) Speaker: A. Alimonti. Abstract: A. Alimonti, F. Satta, M. Di Palma, G. Ferretti, P. Piergrossi, G. Codacci-Pisanelli, V. Zoffoli, F. Todi and I. Pavese .The impact of cytokines circulating levels on cancer-related-fatigue. Proc. Amer. Assoc. Cancer Res, Volume 45, 2004]Abstract#1400 2003 American Society of Clinical Oncology (ASCO) Abstract: Alimonti A. Prevention of irinotecan (CPT-11) + 5- fluorouracil/leucovorin (FU/LV) diarrhea by oral administration of neomycin + bacitracin in first line treatment of advanced colo-rectal cancer. Meeting: 2003 ASCO Annual Meeting Abstract No: 1116 First Author. Virtual Meeting by A. Alimonti. 2000 25th Congress of the European Society for Medical Oncology Abstract: Portalone, Luigi ; Altieri, A. Maria; Alimonti, Andrea; Antilli, Antonio; Nunziati, Francesco ; Perrone, Nicola ; Pronzato, Paolo ; Signora, Mauro. Phase II study: gemcitabine plus epirubicin in malignant pleural mesothelioma. An A.I.P.O. Chest Oncology Study Group trial. 2000 25th Congress of the European Society for Medical Oncology Abstract: Portalone, Luigi; Altieri, A. Maria; Alimonti, Andrea; Antilli, Antonio; Nunziati, Francesco ; Perrone, Nicola; Signora, Mauro. Pamidronate versus radiotherapy in the treatment of bone metastases by lung cancer: A randomized A.I.P.O. Chest Oncology Study Group trial. PART III Bibliography: Original Reports .
1. Nardella C, Lunardi A, Fedele G, Clohessy JG, Alimonti A, Kozma SC, Thomas G, Loda M,
Pandolfi PP. Differential expression of S6K2 dictates tissue-specific requirement for S6K1 in mediating aberrant mTORC1 signaling and tumorigenesis. Cancer Res. 2011 May 15;71(10):3669-75
A. Alimonti, A. Carracedo, J. G. Clohessy, C. Nardella, L. C. Trotman, C. Nardella, A. Egia, L. Salmena, K. Sampieri, E. Brogi, J. Zhang, A. Richardson and P. P. Pandolfi. Subtle variations in Pten dose determine breast cancer susceptibility. Nat Genet. 2010 May;42(5):454-8.
3. A. Alimonti, C. Nardella, Z. Chen, J. G. Clohessy, L. C. Trotman, A. Carracedo, K. Cheng, S.
Varmeh-Ziaie, M. B. Kastan, S.C. Kozma, G. Thomas, E. Rosivatz, R. Woscholski, F.Cognetti, H.I. Scher and P. P. Pandolfi. Modulation of cellular senescence response for ‘pro-senescence’ therapy in cancer. J Clin Invest. 2010 Mar;120(3):681-93.
4. I. Pavese, F. Satta, P.Piergrossi, E. Brunetti & A. Alimonti. High serum levels of TNF-alpha
and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients. Ann Oncol. 2009 Dec 23.
5. Chen Z, Carracedo A, Lin HK, Koutcher JA, Behrendt N, Egia A, Alimonti A, Carver BS,
Gerald W, Teruya-Feldstein J, Loda M, Pandolfi PP. Differential p53-independent outcomes of p19(Arf) loss in oncogenesis Sci Signal. 2009 Aug 18;2(84):ra44.
6. Carver BS, Tran J, Gopalan A, Chen Z, Shaikh S, Carracedo A, Alimonti A, Nardella C,
Varmeh S, Scardino PT, Cordon-Cardo C, Gerald W, Pandolfi PP. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat Genet. 2009 May;41(5):619-24. Epub 2009 Apr 26.
7. Carver BS, Tran J, Chen Z, Carracedo-Perez A, Alimonti A, Nardella C, Gopalan A, Scardino
PT, Cordon-Cardo C, Gerald W, Pandolfi PP. ETS rearrangements and prostate cancer initiation. Nature. 2009 Feb 12;457(7231):E1; discussion E2-3.
8. Nardella C, Carracedo A, Alimonti A, Hobbs RM, Clohessy JG, Chen Z, Egia A, Fornari A,
Fiorentino M, Loda M, Kozma SC, Thomas G, Cordon-Cardo C, Pandolfi PP. Differential requirement of mTOR in postmitotic tissues and tumorigenesis. Sci Signal. 2009 Jan 27;2(55):ra2
9. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT,
Thomas G, Kozma SC, Papa A, Nardella C, Cantley LC, Baselga J, Pandolfi PP. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008 Sep;118(9):3065-74
10. Nardella C, Chen Z, Salmena L, Carracedo A, Alimonti A, Egia A, Carver B, Gerald W,
Cordon-Cardo C, Pandolfi PP. Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events. Genes Dev. 2008 Aug 15;22(16):2172-7
11. X. Wang, L. Trotman, T. Koppie, A. Alimonti, Z. Gao, J. Wang, H. Erdjument-Bromage, P.
Tempst, C. Cordon-Cardo, P.P. Pandolfi and X. Jiang. NEDD 4-1 is the Proto-oncogenic Ubiquitin ligase for PTEN. Cell. 2007 Jan 12;128(1):129-39.
12. L.C. Trotman, X. Wang, A. Alimonti, Z. Chen, J. Teruya-Feldstein, S-G. Chi, H-J. Kim, H.
Yang, N.P. Pavletich, B.S. Carver, H. Erdjument-Bromage, P. Tempst, C. Cordon-Cardo, T.
Misteli. X. Jiang and P.P. Pandolfi. Ubiquitination regulates nuclear PTEN import and tumor suppression as revealed by inherited mutation. Cell. 2007 Jan 12; 128(1): 141-56.
13. L.C. Trotman, A. Alimonti, P.P. Scaglioni, J.A. Koutcher, C. Cordon-Cardo and P.P. Pandolfi.
Identification of a tumour suppressor network opposing nuclear Akt function. Nature, 441:523-7 2006
14. Bernardi R, Guernah I, Jin D, Grisendi S, Alimonti A, Teruya-Feldstein J, Cordon-Cardo C,
Simon MC, Rafii S, Pandolfi PP. PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR. Nature. 2006 Aug 17; 442(7104):779-8
15. Ferretti G, Alimonti A, Cognetti F. Is thymidylate synthase a reliable predictor for response and
survival during hepatic arterial infusion for hepatic metastases from colorectal cancer? Br J Cancer. 2006 Nov 6;95(9):1304-5; author reply 1306-7. Epub 2006 Oct 17
16. Migliore A, Tormenta S, Massafra U, Carloni E, Padalino C, Iannessi F, Alimonti A, Martin
LS, Granata M. Repeated ultrasound-guided intra-articular injections of 40 mg of Hyalgan may be useful in symptomatic relief of hip osteoarthritis. Osteoarthritis Cartilage. 2005 Dec;13(12):1126-7. Epub 2005 Oct 19.
17. Migliore A, Tormenta S, Martin Martin LS, Iannessi F, Massafra U,Carloni E, Monno D,
Alimonti A, Granata M. The symptomatic effects of intra-articular administration of hylan G-F 20 on osteoarthritis of the hip: clinical data of 6 months follow-up. Clin Rheumatol. 2006 May;25(3):389-93. Epub 2005 Oct 25
18. Alimonti A, Ferretti G, Cognetti F. Can the reliance of hormone receptor assays of surgical
specimens be explained by the fluctuation of estrogen receptor, progesterone receptor, and HER-2 protein expression in tumor samples of premenopausal breast cancer patients? J Clin Oncol. 2005 Dec 1;23(34):8918
19. Migliore A, Massafra U, Carloni E, Padalino C, Martin Martin S, Lasaracina F, Dibiase N,
Alimonti A, Granata M. TNF-alpha blockade induce clinical remission in patients affected by polymyalgia rheumatica associated to diabetes mellitus and/or osteoporosis: a seven cases report. Eur Rev Med Pharmacol Sci. 2005 Nov-Dec; 9(6):373-8.
20. Ferretti G, Fabi A, Carlini P, Papaldo P, Cordiali Fei P, Di Cosimo S, Salesi N, Giannarelli D,
Alimonti A, Di Cocco B, D'Agosto G, Bordignon V, Trento E, Cognetti F. Zoledronic-acid- induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients. Oncology. 2005; 69(1): 35-43. Epub 2005 Aug 2.
21. Alimonti A, Nardoni C, Papaldo P, Ferretti G, Caleno MP, Carlini P, Fabi A, Rasio D,
Vecchione A, Cognetti F. Nail disorders in a woman treated with ixabepilone for metastatic breast cancer. Anticancer Res. 2005 Sep-Oct;25(5):3531-2
22. Di Cosimo S, Ferretti G, Papaldo P, Carlini P, Fabi A, Ruggeri EM, Alimonti A, Nardoni C,
Cognetti F. Does the concurrent use of anthracycline and granulocyte colony-stimulating factor influence the risk of secondary leukaemia in breast cancer women? Ann Oncol. 2005 Jul;16(7):1209-10. Epub 2005 Apr 27.
23. Alimonti A, Di Cosimo S, Ferretti G, Sperduti I, Carlini P, Papaldo P, Fabi A, Gelibter A,
Ciccarese M, Giannarelli D, Mandala M, Milella M, Ruggeri EM, Cognetti F. Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer. Ann Oncol. 2004 Jul;15(7):1065-71
24. Migliore A, Tormenta S, Valente C, Massafra U, Martin Martin LS, Carmenini E, Bernardini A,
Alimonti A. Intra-articular treatment with Hylan G-F 20 under ultrasound guidance in hip osteoarthritis. Clinical results after 12 months follow-up. Reumatismo. 2005 Jan-Mar;57(1):36- 43.
25. Migliore A, Tormenta S, Martin LS, Valente C, Massafra U, Granata M, Alimonti A. Open
pilot study of ultrasound-guided intra-articular injection of hylan G-F 20 (Synvisc) in the
treatment of symptomatic hip osteoarthritis. Clin Rheumatol. 2005 Jun;24(3):285-9. Epub 2004 Dec 9.
26. Ferretti G, Di Cosimo S, Giannarelli D, Papaldo P, Alimonti A, et al. Endocrine adjuvant
therapy and Her-2 neu over-expression: Can muddy water become clear ? JCO 2004 February
27. Migliore A, Tormenta S, Martin Martin LS, Valente C, Massafra U, Latini A, Alimonti A.
Safety profile of 185 ultrasound-guided intra-articular injections for treatment of rheumatic diseases of the hip. Reumatismo. 2004 Apr-Jun;56(2):104-9.
28. Alimonti A, Di Cosimo S, Di Palma M, Ferretti G, Vecchione A. Is video-assisted thoracic
surgery always safe? Minerva Chir. 2004 Aug;59(4):413-4
29. Alimonti A. et al. May colorectal cancer patients with Thymidylate-Sintetase positive liver
metastases have an overall survival advantage by hepatyc arterial infusion alone? J Clin Oncol. 2003 Sep 15;21(18):3543-4
30. Alimonti A. et al "A woman with subacute motor weakness and left renal mass". Am J Med.
31. Alimonti A. et al. A man with a deltoid mass and erythrocytosis: case report and review of the
cases. Anticancer Res. 2003 Nov-Dec; 23(6D):5181-4.
32. Martin-Martin LS, Latini A, Pagano A, Ragno A, Stasi R, Coppe A, Davoli G, Crescenzi A,
Alimonti A, Migliore A. A new mathematical model based on clinical and laboratory variables for the diagnosis of Sjogren's syndrome. Clin Rheumatol. 2003 May;22(2):123-124
33. Alimonti A et al. Prevention of irinotecan plus 5-fluorouracil/leucovorin-induced diarrhoea by
oral administration of neomycin plus bacitracin in first-line treatment of advanced colorectal cancer. Ann. Oncol 2003 14: 805-a-806-a
34. Migliore A, Martin LS, Alimonti A, Valente C, Tormenta S. Efficacy and safety of
viscosupplementation by ultrasound-guided intra-articular injection in osteoarthritis of the hip. Osteoarthritis Cartilage. 2003 Apr;11(4):305-6
35. Alimonti A, et al. New approaches to prevent the intestinal toxicity of irinotecan-based
regimens. Cancer Treat Rev. 2004 Oct;30(6):555-62. Review.
36. Di Cosimo S, i Ferretti G, Fazio N, Silvestris N, Carlini P, Alimonti A, et al. Docetaxel in
Advanced Gastric Cancer. Acta Oncologica Volume 42, Number 7 / November 2003.
Reviews and Monographs:
1. Nardella C, Clohessy JG, Alimonti A, Panodlfi PP. Pro-senescence therapy for cancer treatment.
Nat Rev Cancer. 2011 Jun 24;11(7):503-11.
2. Carracedo A, Alimonti A, Pandolfi PP.PTEN level in tumor suppression: how much is too
little?Cancer Res 2011 Feb 1;71(3):629-33
3. Andrea Alimonti, Alain Gelibter, Ida Pavese, Francesco Satta, Gianluigi Ferretti, Francesco
Cognetti, and Mario Di Palma. New approaches to prevent the intestinal toxicity of irinotecan-based regimens. Cancer Treat Rev. 2004 Oct; 30(6):555-62. Review.
4. Alimonti A, Monorchio A, Quirino N, Alimonti P. Ambiente, inquinamento da autoveicoli e
patologie respiratorie: costi sanitari, socio-economici e possibili soluzioni. An Ageing Society dossier. Ageing and Health study Group
5. Serena Di Cosimo, Gianluigi Ferretti, Nicola Fazio, Nicola Silvestris, Paolo Carlini, Andrea Alimonti, Alain Gelibter Alessandra Felici, Paola Papaldo, Francesco Cognetti. Docetaxel in Advanced Gastric Cancer. Acta Oncologica Volume 42, Number 7 / November 2003
Title: “Notions of Evil Today: Perspectives of Sixth Graders in Manila”The 3rd SSEASR Conference in Bali, Indonesia Theme: “Waters in South and Southeast Asia: Interaction of Culture and Religion”, June The challenge of finding out the relevance of traditional religious notions remains a fresh concern for the local church in the Philippines, a predominantly Christian nation in the hear
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